Diagnostic Considerations

Acute polio

Chronic inflammatory myopathies

Malignancy

Metabolic and congential myopathies

Mixed connective-tissue disease

Polyarteritis

Primary lateral sclerosis

Rheumatoid arthritis

Steroid-induced myopathy

Duchenne muscular dystrophy: Duchenne or Becker dystrophies tend to manifest in childhood with a male predominance, calf hypertrophy, scoliosis, and marked elevation of CK levels. Sex-linked recessive inheritance and the demonstration of absence or alteration of dystrophin confirm the diagnosis of these disorders. Approximately 60% of cases are sporadic; thus, muscle biopsy is an important diagnostic tool.

Scleroderma, polymyositis, and dermatomyositis: Differentiation from scleroderma, polymyositis, and dermatomyositis may be made by their clinical courses, which are often characterized by more rapid progression, involvement of skin and neck muscles, and dysphagia.

Polymyositis: Electromyography (EMG) in patients with polymyositis reveals polyphasic and fibrillation potentials, as well as myopathic potentials and positive sharp waves. A clinical response to steroids solidifies the diagnosis of polymyositis.

Chronic spinal muscular atrophy: This is another entity that can have proximal weakness and elevated CK levels; however, neurogenic changes seen during EMG may include fibrillation and fasciculation potentials and a reduced recruitment pattern, as well as giant action potentials. Muscle biopsy results showing target fibers and group atrophy with angular fibers also help confirm this diagnosis.

Metabolic and congenital myopathies (eg, central core disease, nemaline centronuclear myopathy, congenital fiber-type disproportion): These may appear clinically similar to limb-girdle muscular dystrophy (LGMD) syndrome, but all of these conditions have typical diagnostic muscle biopsy findings that show central cores, nemaline rods, centronuclear fibers of congenital fiber-type disproportions, and sarcoplasmic body myopathy. Onset is also generally at an early age, and a more diffuse distribution of weakness occurs.

In summary, evaluation of a patient with LGMD syndrome must take into consideration an accurate clinical history with special emphasis on family history; a detailed physical examination; laboratory investigation, including CK; EMG; and possibly, muscle biopsy, molecular genetic studies, and an evaluation of the absence or alteration of dystrophin.

Dystrophin-glycoprotein complex bridges the inner cytoskeleton (F-actin) and the basal lamina. Mutations in all sarcoglycans, in dysferlin, and in caveolin-3, as well as mutations that cause abnormal glycosylation of alpha-dystroglycan, can result in limb-girdle muscular dystrophy.

The authors and editors of Medscape Reference wish to thank Suneet Sahgal, MD, Staff Physician, Department of Physical Medicine and Rehabilitation, Northwestern University Medical School, for his previous contribution to this article.